1. Field of the Invention
The present invention relates to compositions and methods of using same to direct an immune response thereby enhancing the efficacy of an antigen containing vaccine by combining a chemokine in conjunction with the vaccine, wherein the choice of the chemokine directs the immune response in either the Th1 or Th2 direction.
2. Background of the Related Art
Immunization procedures often are made more effective by delivering immnunogens along with empirical preparations defined as adjuvants. These preparations have the effect of enhancing immune response by improving antigen presentation, essentially by inducing local innate immune responses, that in-turn increase expression of co-stimulatory molecules and cytokines that stimulate T cells growth and differentiation and recall antigen-presenting cells at the site of immunization. In recent times several investigators have tried to enhance antigen presentation by introducing immuno-stimulatory cytokines along with the immunogen [1], [2] and [3]. A similar approach has been attempted to manipulate T helper response towards cellular (Th1) or humoral (Th2) immunity [3]. These studies reflect the intent to rationally induce and modulate immune response in a targeted, rather than in an empirical manner. Chemoattractant cytokines, or chemokines (CC), function as immunologic mediators by attracting specific subsets of leukocytes to either sites of inflammation (inflammatory cytokines) or, when involved in homing processes, to lymphoid organs, (constitutively expressed cytokines) [4]. Therefore, chemokines are relevant to the pathogenesis of many diseases such as chronic infections, inflammatory and autoimmune diseases, transplant rejection, and cancer [5], [6] and [7]. Further, chemokines and their receptors are also involved in the selective induction of both Th1 and Th2 responses [4].
In early studies, RANTES was found to enhance immunity to HIV in DNA vaccines [8] and [9] whereas MCP-1 DNA appeared to be an effective means of boosting immune responses against experimental tumors [10]. In addition, chemokines and antigens have been linked to create new, more potent immunogens [11] and [12]. However, studies comparing the effects of different chemokines on immune response profiles to a specific antigen have not been conducted. DNA immunization is presently being developed as an inexpensive and safe means for providing immunizations to large numbers of people. One of the shortcomings of this approach is the relatively weak immune response triggered by DNA vaccines. The present invention provides for the administration of select chemokines to enhance the immune response to DNA vaccines.
Because of their ability to attract discrete sub-populations of leukocytes to sites of inflammation and antigen presentation, chemokines are key agents in eliciting immune responses. In addition, chemokines reportedly can influence the T helper response towards a Th1 (i.e. cell mediated) or Th2 (i.e. humoral) profile, according to the differential distribution of receptors on target cells.
Therefore, the use of chemokines in immunization may contribute a tailored adjuvant-like effect. In addition, since some diseases are known to significantly alter the Th profile of the immune response, vaccination programs in areas endemic for such diseases can be hampered by the prevalence of a skewed immune response. The use of chemokines in adjuvant preparation has the potential to rebalance the immune response, thus, improving the success rate of a vaccination program in this context.